Novel circulating biomarker digital scores for assessing treatment response in liver cancer

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PROJECT SUMMARY/ABSTRACT Ju Dong Yang, MD, MS is a faculty in the Karsh Division of Gastroenterology and Hepatology and the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center and a health sciences assistant clinical professor at the University of California, Los Angeles. Dr. Yang`s long-term career goal is to become a physician-scientist in precision medicine-based diagnosis and treatment of hepatocellular carcinoma (HCC). Dr. Yang`s long-term research objective is to translate novel biomarker discovery into clinical practice by determining the utility of novel liquid biopsy technology in early detection of cancer development and progression, assessment and prediction of treatment response, and prognosis. To achieve his long-term career goal and research objectives, Dr. Yang set up short-term career goals of gaining skills in 1) liquid biopsy biotechnologies, 2) prospective patient recruitment and monitoring, 3) advanced biostatistics for longitudinal data analysis, and bioinformatics for large scale transcriptomic data analysis and marker panel selection, and 4) leadership and research grant writing. HCC is a biologically aggressive tumor and one of the leading causes of cancer-related deaths worldwide. Following cancer treatment, patients undergo radiologic tests for evaluation of treatment response. However, post-treatment radiologic assessment could be obscured due to treatment- related non-specific changes. The main objective of Dr. Yang's K08 proposal is to investigate the performance of novel circulating biomarker digital scores for evaluation of HCC treatment response. Recently, Dr. Tseng (Co-Primary mentor) has developed a streamlined HCC extracellular vesicles (EV) digital scoring assay that couples two robust technologies, i.e., EV Click Chip for purification of HCC EVs and reverse-transcription droplet digital PCR (RT-ddPCR) for quantification of HCC-specific mRNA markers with outstanding performance for early-stage HCC detection. Dr. Yang demonstrated that the GALAD score, derived from three HCC protein tumor markers (AFP-L3, AFP, and Des-carboxyprothrombin) is highly accurate for the detection of early-stage HCC. Both scores reflect tumor burden and our pilot data showed their promising performance in assessing treatment response. Thus, the central hypothesis of the project is that pre- and post-treatment HCC EV digital score, GALAD score, and integration of two independent scores (i.e., HCC EV-GALAD digital score) can evaluate HCC treatment response. Dr. Yang will conduct phase 2 and 3 biomarker studies to test the hypothesis. For successful completion of the project and career development, Dr. Yang assembled a mentoring committee consisting of Shelly Lu, M.D. (Primary mentor, HCC biology); Hsian-Rong Tseng, Ph.D. (Co-Primary mentor, HCC EV technology); Edwin Posadas, M.D., Amit Singal, M.D. (Co-mentor, prospective patient enrollment and monitoring), Sungyong You, Ph.D. (Co-mentor, bioinformatics) and Mourad Tighiouart, Ph.D. (Co-mentor, biostatistics). This K08 award will allow Dr. Yang to gain news skills while conducting a novel circulating tumor biomarker study to address urgent clinical unmet needs in HCC.